The H-2 system is a complex of genes involved in transplantation, immune response to thymus-dependent antigens, resistance and susceptibility to tumor viruses and production of certain serum proteins. The system is highly polymorphic. In the proposed program, the extent of the H-2 polymorphism will be determined by serological analysis of wild mice. Congenic lines carrying wild-derived H-2 chromosomes on a genetically homogeneous background will be developed and used for preparation of a battery of antisera directed against wild-derived H-2 antigens. The antisera will then be used for serological characterization of samples of wild mice populations. The role of linked loci (t-factors) and of the population structure in maintainance of the H-2 polymorphism will be studied in a series of population cage experiments. An attempt will be made to obtain some notion about the biological and evolutionary significance of the H-2 polymorphism by studying the function and functional interrelationship of individual H-2 genes.